ธต สนบบญ

อายรศาสตร แพทยศาสตร

14 ตลาคม 61

Reproductive Endocrine Disorders And

Short/Tall stature

Amenorrhea/Hirsutism

Male Hypogonadism/Gynecomastia

Short/Tall Stature

Cases

• Primary (14/16) or Secondary (3/6)

• Primary: 2o sex + pelvic exam/chromosome (XY)

- low E (XO)

• Secondary: hirsutism/hypo E/systemic illness/pregnancy

- Pituitary tumor/Ovarian failure

- Androgen excess

Amenorrhea

Endocr Rev 2002; 23:120-140

Turner syndrome: Physical signs

Insulin resistance & DM type 2 AITD 22% thyroid Ab check thyroid Ab, TSH at 10 y; Ab+ve (TSH annually) Inflammatory bowel disease Hepatic disease Malignancy: gonadoblastoma (45,X/46,XY) Otological disorders: conductive & neurosensory hearing loss Horseshoe kidney

Turner syndrome

HRT in Turner syndrome

Follow up

Approach as 2nd amenorrhea

Am Fam Physician 2006; 73: 1374-1382.

Best Pract Res Clin Obstet Gynaecol 2003; 17: 75-92.

Hirsutism

Hirsutism

Hatch R, et al. Am J Obstet Gynecol 1981; 140: 815-30.

Rosenfield RL. NEJM 2005; 352: 2578-88.

> 7

Testing androgen levels in women when

1. Moderate or severe Hirsutism (Score >15) 2. Hirsutism with sudden onset, rapidly progressive 3. Hirsutism with Virilization Acne, Alopecia, Baldness Menstrual dysfunction and/or infertility Central obesity Acanthosis nigricans

Martin KA, et al. JCEM 2008; 93: 1105-1120.

Step 1: Drug use, Severity: mild (8-15) Idiopathic hirsutism Rx

Step 2: Severity: moderate or more (>15)

Virilization, PCOS risk, Neoplasm risk, other endocrinopathy risk

Hirsutism

Deepening of voice

Increased libido

Androgenic muscle development

Masculine habitus

Breast atrophy, Abnormal Menstruation

Clitoromegaly

Acne

Virilization

NIH criteria (1990) Hyperandrogenism/-emia

Oligo-ovulation

Exclusion of related disorders

ESHRE/ASRM criteria (2003)

Clinical and/or biochemical hyperandrogenism

Oligo- or anovulation

PCO

Exclusion of related disorders

Testis: 1.5 x 1 cm both (2 ml, soft, no mass)

Length of penis 2.5 cm, No pubic/axillary hair

Eunuchoid appearance

High-pitched voice

M: 22-year-old, delayed puberty

• Sexual development, Eunuchoidism • Reduced sexual desire (libido) • Decreased spontaneous erections • Low/zero sperm counts, Infertility • Loss of body (axillary, pubic) hair • Gynecomastia • Small testes (< 5 mL) • Male osteoporosis • Reduced muscle bulk and strength • Hot flashes, sweats

ประวต ตรวจรางกาย

Secondary sexual characteristics

Testicular examination: size and consistency

Body mass index (BMI)/Waist circumference

Body proportions (e.g. female fat distribution)

Pubic hair (density, distribution)/Penis (size)/Scrotum (pigmentation)

Gynecomastia

Smell test, Midline defect, Teeth, CNS, Kidney

Young J. JCEM 2012; 97: 707-718.

Endocrine Society 2008

Endocrine Society 2010

FSH 0.22 IU/L (1-8.4)

LH 3.0 IU/L (1-10.5)

Testosterone 2.5 (<10 nmol/L)

FT4 1.29 ng/dL (0.8-1.8)

TSH 0.55 uU/mL (0.3-4.1)

Morning cortisol 8.3 ug%

IGF-1 213 ng/mL (47-318)

Genital defects

Neurological defects Somatic defect

Microphallus

Cryptorchidism

ANOSMIA/HYPOSMIA

Nystagmus

SNHL

Cerebellar ataxia

Spastic paraplegia

Leaning disability

Color blindness

Synkinesia

Seizures

Cleft lip

Cleft palate

High arch palate

Dental agenesis

Renal agenesis

Horseshoe kidney

Pes cavus

Kallmann syndrome

CORONAL T1W and T2W

Olfactory sulci

Olfactory bulbs/tracts

• ออนเพลย 6 เดอน ปรกษาแพทยเรอง ชายวยทอง

• T: 8.2, 7.9 nmol/L, FSH: 9.7 IU/L (1.0-8.4), LH: 4.7 IU/L (1.0-10.5)

• วนจฉย andropause andriol 80 mg/d

• อาการดขน แตยงรสกมไข รอนวบวาบ andriol 240 mg/d

• T: 13.2 nmol/L

• ปรกษาเรองการเลอกใชยา

• BT 38.2oc น าหนก 78 64 กโลกรม

• Infective endocarditis

• T: 16.7 nmol/L

M: 46-year-old, fatigue

Male hormone

Gooren LG, et al. Drugs 2004; 64: 1861-1891.

T levels in different forms

Endocr Pract 2002

Management

Gynecomastia ชาย 20 ป เรองเตานมโต

Breast mass

Lipomastia Breast cancer

Metastasis

Onset (1 ป)

Tenderness

Unilateral/Bilateral

Discharge/Galactorrhea

Axillary lymph node

Cancer risks

2 cm Nipple-Areloar Complex

Bilateral 50%

Macrogynecomastia

NEJM 2007

J Plast Reconst & Aesthet Surg 2008; 61: 41-49

Progesterone

Gynecomastia

Physiology Pathology

Neonatal

Puberty

Elderly

Drugs (20-25%)

Systemic diseases

Estrogen excess

Hypogonadism

Idiopathic

(25%)

NEJM 2007

Expert Opin Drug Saf 2012

Systemic diseases

• Endocrine disease: GH, Cortisol, Thyroid (10-40%), Prl • Failure: Liver (8%), Renal (1%) • Neurological diseases: Myotonic dystrophy, Kennedy syndrome • HIV • Starvation, Refeeding • NF-1, PJS • Prostatic cancer

Laboratory assessment

b-hCG USG testis

Testosterone, Estrogen Prolactin

hypogonadism FSH, LH

hyperestrogenemia Testis or Adrenal or Aromatase

Thyroid function test

Liver or Renal failure

ชาย 20 ป เตานมโตทง 2 ขาง บตร คนเดยว แรกเกด 2,600 g พฒนาการปกต

เตานมโตตงแตอายประมาณ 14 ป ไมเจบ ไมมน านมไหล

ไมดมสรา/ยาเสพตด

morning erection 2-3 ครง/สปดาห ยงไมเคยมเพศสมพนธ

170 cm (expected height 167 cm), arm span 171 cm, 60 kg

Testes 3 cm in diameter, 2nd sex characteristics: well-developed

Public hair: male pattern Tanner IV

Prolactin: 6.0 ng/mL < 2-25> FSH: 2.7 IU/L <1.0-8.4> LH: 4.7 IU/L <1.0-10.5> Testosterone: 26.1 nmol/L <5.9-24.7> Estradiol: 155.5 pmol/L <0-130> Free androgen index: 32.4% <40-90>

Pseudogynecomastia หรอ Obvious causative drugs/conditions

Provide assurance, Remove/Treat cause, Provide periodic follow-up

Palpable Scrotal mass Testicular US

ประวตและตรวจรางกาย

Gynecomastia

Suspect breast mass

(hard, eccentric) USG หรอ Mammography และ Biopsy

Liver หรอ Renal หรอ Thyroid disease

LFTs, Renal function, and TSH assays

Treat underlying disease

Hormone testing ( total and bioavailable T,E2 , prolactin, LH , hCG assays)

T T ↑hCG

Hypogonadism

Androgen resistance

Testicular US

↑Prolactin

MRI pituitary

Germ cell tumor

Normal

Extragonadal hCG-secreting tumors

(bronchogenic, hepatic)

Pituitary disease

↑E2

Testicular US

Mass (Leydig หรอ

Sertoli cell tumor)

Normal

CT abdomen

Adrenal neoplasm

Normal

Increased aromatase activity

Exogenous estrogens

Negative work-up

Idiopathic

gynecomastia

15 CAG

52 CAG

31 CAG

Sequencing : CAG repeats of the AR gene

“คณ ตา (73 ป) และ นา (35 ป)” เตานมโต และเดนไมคอยคลอง

Kennedy syndrome • Spinal and Bulbar Muscular Atrophy (SBMA)

• CAG triplet (repeats) or polyglutamine disease : Huntington’s disease, dentatorubral-pallidoluysian atroph, spinocerebellar ataxia (5 subtypes)

• X-linked), female carriers (muscle cramps)

• Androgen receptor, exon 1, Positive correlation with severity

• Onset: ages 18-64, the 4th- 5th decade

• Time to diagnosis: 3 years

• Progress slowly, Normal life span

• 1-2/100,000, limited awareness

J Neurol Neurosurg Psychiatry 2018;

Neurological manifestations • Tremor, cramping, proximal/distal muscle weakness and atrophy

lower motor neuron degeneration, primary muscle atrophy

• Bulbar muscle involvement dysarthria, dysphagia, hypernasality, decreased range of pitch and loudness, perioral fasciculation

• Temporalis/Masseter muscles weakness chewing, jaw drop

• A loss of sensation in the lower extremities (DRA)

• EMG/NCV: Low sensory nerve amplitudes, Decreased compound motor action potentials, Diffuse denervation. Motor unit nerve estimation (MUNE) is reduced to about half of healthy control values.

• Muscle biopsy: neurogenic/myogenic atrophy J Neurol Neurosurg Psychiatry 2018;

ชาย 40 ป กอนทเตานมขวามา 3 เดอน

กอนโตเรว ไมเจบ ไมมน านมไหล

กนยาแกไขเปนประจ า

ไมดมสรา หรอ ใชยาเสพตด

morning erection ปกต

โรคประจ าตว NHL remission (3 ป)

4(6) cm (macrogynecomastia)/Tanner III >1 year

Breast cancer Patient prefer

Surgery

Short/Tall Stature

ขอมลทตองการ

1. Height, Weight, Arm span, Nutritional status

2. Height velocity: Growth chart

3. Mid parental height: Expected height

4. Body proportion: Proportionate, Disproportionate

5. Bone age

ประวต

• Child heath, Maternal health, IUGR

• Development

• Illness or chronic diseases, psychological stress

• Puberty

• Family history

• Growth curves: height age, weight age

การตรวจรางกาย

• Upper/Lower ratio

• Arm span

• Weight

• Head circumferences

• Secondary sex characteristics

ธนน สหกจรงเรอง